By the relatively new technique of Electrospray Ionization (ESI) it is now possible to transform intact large, complex and fragile molecular species from solutes in solution to ions in vacuum. Moreover, even when they have molecular weights (M's) as high as 5,000,000, these ions carry so many charges that they can be readily "weighed" with relatively inexpensive instruments such as quadrupole mass filters and ion traps. Consequently, the sensitivity, accuracy and selectivity of mass spectrometry (MS) is now being increasingly applied to the difficult analytical problems of bio science and medicine. In spite of an explosion of interest and activity in ESMS, the mechanisms of many of its component processes are not at all well understood. The proposed research is aimed at understanding these mechanisms so that the inherent promise of the technique can be fulfilled. One major task to be undertaken will use experiments and theory to elucidate the still mysterious process by which solute ions are formed from the tiny charged droplets produced by electrostatic dispersion of sample solution. A second task will be to study the response of multiplier detectors to the multiply charged ions that ESI produces. These ions are so new to the laboratory scene that their properties and behavior are virtually unknown. The third major effort will be a collaboration with two groups in the Medical School aimed at applying the power of ESMS to (a) the analysis of reactants, intermediates and products involved in brain chemistry and (b) to identify and characterize non-covalently-bound complexes of species that are important in immunological function and behavior.